Journal of Inherited Metabolic Disease

, Volume 34, Issue 1, pp 225–231

Harderoporphyria due to homozygosity for coproporphyrinogen oxidase missense mutation H327R

  • Alev Hasanoglu
  • Manisha Balwani
  • Çiğdem S. Kasapkara
  • Fatih S. Ezgü
  • İlyas Okur
  • Leyla Tümer
  • Alpay Çakmak
  • Irina Nazarenko
  • Chunli Yu
  • Sonia Clavero
  • David F. Bishop
  • Robert J. Desnick
Original Article

Abstract

Hereditary coproporphyria (HCP) is an autosomal dominant acute hepatic porphyria due to the half-normal activity of the heme biosynthetic enzyme, coproporphyrinogen oxidase (CPOX). The enzyme catalyzes the step-wise oxidative decarboxylation of the heme precursor, coproporphyrinogen III, to protoporphyrinogen IX via a tricarboxylic intermediate, harderoporphyrinogen. In autosomal dominant HCP, the deficient enzymatic activity results primarily in the accumulation of coproporphyrin III. To date, only a few homozygous HCP patients have been described, most having Harderoporphyria, a rare variant due to specific CPOX mutations that alter enzyme residues D400–K404, most patients described to date having at least one K404E allele. Here, we describe a Turkish male infant, the product of a consanguineous union, who presented with the Harderoporphyria phenotype including neonatal hyperbilirubinemia, hemolytic anemia, hepatosplenomegaly, and skin lesions when exposed to UV light. He was homoallelic for the CPOX missense mutation, c.980A>G (p.H327R), and had massively increased urinary uroporphyrins I and III (9,250 and 2,910 μM, respectively) and coproporphyrins I and III (895 and 19,400 μM, respectively). The patient expired at 5 months of age from an apparent acute neurologic porphyric attack. Structural studies predicted that p.H327R interacts with residue W399 in the CPOX active site, thereby accounting for the Harderoporphyria phenotype.

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Copyright information

© SSIEM and Springer 2010

Authors and Affiliations

  • Alev Hasanoglu
    • 1
  • Manisha Balwani
    • 2
  • Çiğdem S. Kasapkara
    • 1
  • Fatih S. Ezgü
    • 1
  • İlyas Okur
    • 1
  • Leyla Tümer
    • 1
  • Alpay Çakmak
    • 3
  • Irina Nazarenko
    • 2
  • Chunli Yu
    • 2
  • Sonia Clavero
    • 2
  • David F. Bishop
    • 2
  • Robert J. Desnick
    • 2
  1. 1.Department of Pediatric Metabolism and NutritionGazi University HospitalAnkaraTurkey
  2. 2.Department of Genetics and Genomic SciencesMount Sinai School of Medicine of New York UniversityNew YorkUSA
  3. 3.Department of PediatricsMedical School of Harran UniversitySanliurfaTurkey

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